How to Cite this Article: Abdel-Salam GMH, Abdel-Hamid MS, Saleem SN, Ahmed MKH, Issa M, Effat LK, Kayed HF, Zaki MS, Gaber KR. 2012. Profound microcephaly, primordial dwarfism with developmental brain malformations: A new syndrome. Am J Med Genet Part A. 158A:1823–1831.
Profound microcephaly, primordial dwarfism with developmental brain malformations: A new syndrome†
Article first published online: 11 JUL 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 8, pages 1823–1831, August 2012
How to Cite
Abdel-Salam, G. M.H., Abdel-Hamid, M. S., Saleem, S. N., Ahmed, M. K.H., Issa, M., Effat, L. K., Kayed, H. F., Zaki, M. S. and Gaber, K. R. (2012), Profound microcephaly, primordial dwarfism with developmental brain malformations: A new syndrome. Am. J. Med. Genet., 158A: 1823–1831. doi: 10.1002/ajmg.a.35480
- Issue published online: 19 JUL 2012
- Article first published online: 11 JUL 2012
- Manuscript Accepted: 23 APR 2012
- Manuscript Received: 13 MAR 2012
- lethal microcephaly;
- interhemispheric cyst;
- fetal magnetic resonance imaging;
- autosomal recessive inheritance;
- microcephalic osteodysplastic primordial dwarfism;
- Amish microcephaly;
We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. © 2012 Wiley Periodicals, Inc.